We are searching for genetic linkage between genes that contribute to the predisposition to alcoholism and related behaviors using over 500 highly polymorphic DNA marker loci that span the human genome. To date, we have completed over 200,000 locus typings, primarily on Southwestern American Indians and Finns. We have performed a whole autosomal genome scan for genetic linkage to alcohol dependence in the Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite loci and clinical evaluations were available for 152 subjects belonging to extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for linkage emerged for two genomic regions; both regions harbor neurogenetic candidate genes. The best evidence is seen with D11S1984 on chromosome 11p, in close proximity to the DRD4 dopamine receptor gene. Good evidence is seen with D4S3242 on chromosome 4p, nearby the beta1 GABA receptor gene. In Finns, we have investigated autosomal and Y chromosome DNA variability in relation to the Tridimensional Personality Questionnaire (TPQ) and alcohol dependence and antisocial personality disorder (ASPD). For the autosomal genes, we find evidence for genetic linkage and association between ASPD with alcoholism and the chromosome 6 marker locus D6S286. We also find evidence for linkage and association between ASPD with alcoholism and a polymorphism in the closely linked serotoinin receptor gene HTR1B. With regard to the Y chromosome, we find a significant association with alcohol dependence or abuse and three groups of Y chromosomes that are closely related by their mutational histories.